Plaque Psoriasis
Conditions
Keywords
Psoriasis, interleukin (IL) 17A, IL-17A, secukinumab, AIN457, Narrow-band ultraviolet light B, nb-UVB, Psoriasis area and severity index, PASI
Brief summary
The purpose of this study was to determine whether early intervention with subcutaneous (s.c.) secukinumab 300 mg in patients with new-onset moderate to severe plaque psoriasis may lead to prolonged symptom-free periods by preventing reactivation of old lesions or ultimately totally hindering the occurrence of new lesions, i.e., changing the natural course of the disease (Main Study).
Detailed description
This was and open label, parallel group, multicenter, randomized study with 3 clinical periods: Screening period, Treatment period, and Follow-up period. The design consisted of the Main Study and a Mechanistic Sub study: 1. The Main Study had 2-treatment-arm secukinumab and nb-UVB). 2. The Mechanistic Sub-study had 4 arms treated with secukinumab and one arm with nb-UVB arm. The outcome measures were all exploratory, i.e. no results presented. Not all participants of the Mechanistic Sub-study participated in the Main Study, these participants are only reported for the safety analyses, but not for the primary and secondary outcome measures.
Interventions
BIOLOGICALSecukinumab
Secukinumab (AIN457) 300 mg was administered in an open-label fashion according to label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled syringe). Each 300-mg dose was provided as 2 pre-filled syringes of 150-mg secukinumab in a single box. Each syringe was labeled as AIN457 150 mg/1 mL.
RADIATIONnb-UVB
Narrow-band UVB applied in 1 or 2 cycles, each comprising a period of 12 weeks with 2 to 3 treatment sessions per week totaling 24 to 36 sessions per cycle. The application was performed according to the investigational site's protocol, taking into account the patient's skin type. A maximum dose of 3 J/cm2 on the body and 1 J/cm2 on the face was recommended
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Able to understand and communicate with the investigator, willing and capable to comply with all study procedures, and provide written signed and dated informed consent (personally or by a witness) before any assessment is performed. * Aged 18 to 50 years inclusive. * New-onset plaque psoriasis with appearance of the first psoriasis plaques within the last 12 months before randomization and naïve to any systemic treatment and phototherapy (Arm A1, Arm A2, and Arm B1). Episodes of mild psoriasis, which occurred at least 3 years before screening and resolved spontaneously within 6 months will be accepted. * Chronic plaque psoriasis with appearance of the first psoriasis symptoms 5 years or longer and intolerance or inadequate response to phototherapy or any systemic treatment including biologicals, except for IL-17A inhibitors (Arm C1 and Arm C2). * Moderate to severe plaque psoriasis defined at screening and baseline by PASI \>= 10, and body surface area (BSA) \>= 10%, and IGA mod 2011 \>= 3. Key
Exclusion criteria
* Forms of psoriasis other than plaque-type (e.g., pustular, erythrodermic, guttate, light sensitive, and drug induced). * Ongoing use of prohibited treatments. * Previous treatment with phototherapy or any systemic treatment. * Pregnant or nursing (lactating) women. * Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the Treatment period or longer if required by locally approved prescribing information (e.g., 20 weeks in the EU and countries where applicable for secukinumab).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Pain Assessment Severity Index (PASI) 90 at Week 52. | Baseline, Week 52 | The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percent of Body Surface Area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI composite score varies in increments of 0.1 and range from 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. PASI 90 response is a binary measure defined as at least a 90% improvement in PASI score at Week 52, relative to baseline PASI score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved PASI 90 at Week 104 | Baseline, Week 104 | The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percent of Body Surface Area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI composite score varies in increments of 0.1 and range from 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. PASI 90 response is a binary measure defined as at least a 90% improvement in PASI score at Week 104, relative to baseline PASI score. |
| Number of Participants With IGA Mod 2011 0/1 Response at Week 52 | Baseline, Week 52 | Investigators assessed the disease using the validated Investigator Global Assessment (IGA) mod 2011 and rated the disease from a score of 0 (clear skin) to 4 (severe disease). Response is defined as a score of 0 or 1 at Week 52. |
Countries
Argentina, Bulgaria, Canada, Denmark, Estonia, Finland, Germany, Hungary, Poland, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Recruitment details
Subjects were enrolled in 2 study sites in Argentina, 4 in Bulgaria, 2 in Canada, 4 in Germany, 1 in Denmark, 3 in Estonia, 2 in Finland, 2 in Hungary, 6 in Poland, 8 in Spain, 2 in Sweden, 1 in Switzerland, and 4 in the United Kingdom.
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 300 mg Eligible patients received 300 mg secukinumab by subcutaneous (s.c.) injection at baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 48 inclusive (treatment duration = 52 weeks) OR every 4 weeks until Week 100 inclusive (last dose administered at Week 100) (treatment duration = 104 weeks). | 116 |
| Narrow-band Ultraviolet B (Nb-UVB) Eligible patients received 1 or 2 cycles of narrow-band ultraviolet B (nb-UVB) of 12 weeks each with a maximum break of 28 weeks between cycles (patients with PASI 90 at Week 40 will not receive a second treatment cycle) (treatment duration = 52 weeks). | 80 |
| Total | 196 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Disease relapse | 32 | 7 |
| Follow-up Period | Lack of Efficacy | 1 | 2 |
| Follow-up Period | Lost to Follow-up | 4 | 6 |
| Follow-up Period | Physician Decision | 2 | 2 |
| Follow-up Period | Protocol Violation | 1 | 2 |
| Follow-up Period | Study terminated by Sponsor | 6 | 3 |
| Follow-up Period | Subject/guardian decision | 14 | 9 |
| Treatment Period | Adverse Event | 0 | 2 |
| Treatment Period | Lack of Efficacy | 1 | 6 |
| Treatment Period | Lost to Follow-up | 1 | 6 |
| Treatment Period | Physician Decision | 0 | 1 |
| Treatment Period | Subject/guardian decision | 8 | 15 |
| Treatment Period | Subjects not treated | 3 | 4 |
Baseline characteristics
| Characteristic | Secukinumab 300 mg | Narrow-band Ultraviolet B (Nb-UVB) | Total |
|---|---|---|---|
| Age, Customized 18 to 30 years | 56 Participants | 30 Participants | 86 Participants |
| Age, Customized 31 to 50 years | 60 Participants | 50 Participants | 110 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 113 Participants | 72 Participants | 185 Participants |
| Sex: Female, Male Female | 35 Participants | 25 Participants | 60 Participants |
| Sex: Female, Male Male | 81 Participants | 55 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 76 | 0 / 88 | 0 / 76 |
| other Total, other adverse events | 29 / 112 | 8 / 76 | 7 / 88 | 2 / 76 |
| serious Total, serious adverse events | 6 / 112 | 1 / 76 | 0 / 88 | 1 / 76 |
Outcome results
Primary
Number of Participants Who Achieved Pain Assessment Severity Index (PASI) 90 at Week 52.
The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percent of Body Surface Area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI composite score varies in increments of 0.1 and range from 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. PASI 90 response is a binary measure defined as at least a 90% improvement in PASI score at Week 52, relative to baseline PASI score.
Time frame: Baseline, Week 52
Population: Modified Full Analysis Set (mFAS) from the Main Study: all randomized subjects who received at least one dose of study treatment during the Treatment Period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300 mg A1 (A1a+A1b) | Number of Participants Who Achieved Pain Assessment Severity Index (PASI) 90 at Week 52. | 70 Participants |
| Narrow-band Ultraviolet B (Nb-UVB) B1 (B1a+B1b) | Number of Participants Who Achieved Pain Assessment Severity Index (PASI) 90 at Week 52. | 32 Participants |
Comparison: Week 52 PASI 90p-value: <0.000195% CI: [5.9, 48.3]Regression, Logistic
Secondary
Number of Participants Who Achieved PASI 90 at Week 104
The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percent of Body Surface Area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI composite score varies in increments of 0.1 and range from 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. PASI 90 response is a binary measure defined as at least a 90% improvement in PASI score at Week 104, relative to baseline PASI score.
Time frame: Baseline, Week 104
Population: Modified Full Analysis Set (mFAS) from the Main Study: all randomized subjects who received at least one dose of study treatment during the Treatment Period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300 mg A1 (A1a+A1b) | Number of Participants Who Achieved PASI 90 at Week 104 | 23 Participants |
| Narrow-band Ultraviolet B (Nb-UVB) B1 (B1a+B1b) | Number of Participants Who Achieved PASI 90 at Week 104 | 26 Participants |
Comparison: Week 104 PASI 90p-value: 0.65395% CI: [0.3, 2.1]Regression, Logistic
Secondary
Number of Participants With IGA Mod 2011 0/1 Response at Week 52
Investigators assessed the disease using the validated Investigator Global Assessment (IGA) mod 2011 and rated the disease from a score of 0 (clear skin) to 4 (severe disease). Response is defined as a score of 0 or 1 at Week 52.
Time frame: Baseline, Week 52
Population: Modified Full Analysis Set (mFAS) from the Main Study: all randomized subjects who received at least one dose of study treatment during the Treatment Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 300 mg A1 (A1a+A1b) | Number of Participants With IGA Mod 2011 0/1 Response at Week 52 | 85.7 Percentage of participants |
| Narrow-band Ultraviolet B (Nb-UVB) B1 (B1a+B1b) | Number of Participants With IGA Mod 2011 0/1 Response at Week 52 | 36.8 Percentage of participants |